This chapter reviews the epidemiology, disease associations, molecular biology, and pathogenic mechanisms of human T-cell lymphotropic virus (HTLV) types I and II. Association of HTLV-I with two distinct disease processes, a malignancy and a chronic neurologic disorder, spurred worldwide surveys for prevalence of HTLV-I and associated diseases. Transmission of HTLV-I seems to require prolonged, close contact between individuals. Transfer of infected T cells is likely required. The three major reported routes of HTLV-I transmission include sexual intercourse, blood product transmission, and mother-to-child transfer. The most commonly used screening test for HTLV-I/HTLV-II is an enzyme-linked immunosorbent assay (ELISA) which uses a viral lysate-based antigen derived from HTLV-I infection of human T cells. Unlike human immunodeficiency virus (HIV), which has significant genetic differences between isolates, the various HTLV-I strains show a high degree of genetic conservation. There are two major hypotheses for pathogenesis in HTLV-I associated myelopathy (HAM)/tropical spastic paresis (TSP). The first hypothesis is that HTLV-I infects glial cells in the CNS and subsequently induces a cytotoxic immune response against these cells, leading to demyelination. The second hypothesis is that HTLV-I infection activates autoreactive T cells which then cause autoimmune destruction within the CNS (and perhaps in other areas). The molecular biology of HTLV-II is strikingly similar to that of HTLV-I. HTLV-I infection, however, has been linked to several disorders, especially adult T-cell leukemia/lymphoma (ATL) and HAM/TSP. HTLV-I and HTLVII have a similar genetic organization and regulation and share several unique transregulatory proteins.

Model of Tax recruitment of the coactivator CBP to the HTLV-I promoter. For simplicity, only one of the three 21-bp repeats is shown. Tax in association with CREB and the viral CRE creates a high-affinity binding site that anchors CBP to the viral promoter. Once bound, CBP activates HTLV-I transcription through chromatin remodeling and recruitment of the general transcription machinery. TFIIB, transcription factor IIB; P/CAF, p300/CBP-associated factor; RNAP II, RNA polymerase II. (Used with permission from reference 42.)

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10.1128/9781555818289/fig11-4.gif

Figure 4

Model of Tax recruitment of the coactivator CBP to the HTLV-I promoter. For simplicity, only one of the three 21-bp repeats is shown. Tax in association with CREB and the viral CRE creates a high-affinity binding site that anchors CBP to the viral promoter. Once bound, CBP activates HTLV-I transcription through chromatin remodeling and recruitment of the general transcription machinery. TFIIB, transcription factor IIB; P/CAF, p300/CBP-associated factor; RNAP II, RNA polymerase II. (Used with permission from reference 42.)

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